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Synthetic solutions for real-life mysteries

At the Centre for Applied Synthetic Biology, yeast is being used to grow molecules that will prove valuable for health, energy, business and a growing range of fields
May 9, 2016
By Vanessa Bonneau

Scientists have identified 2,500 little-understood plant molecules that are of great pharmaceutical interest — as cancer and heart disease drugs, painkillers, muscle relaxants and cough suppressants. The problem is they aren’t naturally abundant and it has not been easy to make enough of them to properly study their potential medical benefits.

The good news: synthetic biology researchers at Concordia are on the case.

Vincent Martin Vincent Martin, who came to Concordia in 2004, is a professor in the department of biology and the Canada research chair in microbial genomics and engineering. His research could lead to the development of environmentally friendly biofuels.

“We’re really the first-ever centre in Canada to be doing this research,” says Vincent Martin, co-director and co-founder of Concordia’s Centre for Applied Synthetic Biology.

Synthetic biology is the fusion of engineering and more traditional biology. “We know enough — not that much, but enough — in biology that we can start thinking about manipulating it, modifying it, engineering it,” Martin explains.

The centre was founded in 2012, and its 16 members come from a range of Concordia departments including biology, electrical and computer engineering and journalism, and even from other universities across the country.

Martin, a professor in the Department of Biology, leads about a dozen research projects at the centre. His lab includes 13 postdoctoral researchers, research associates and graduate students. In his work, Martin changes the DNA of yeast or bacteria in order to get it to produce molecules with a pharmaceutical or commercial application.

For instance, he leads a number of projects that use natural products to make it faster and cheaper to produce environmentally friendly biofuels. One such project has researchers working to create a strain of yeast that can use the sugars in spent sulfite liquor, a toxic wood pulp by-product, to make ethanol. The research could potentially be used to engineer yeast to generate other biofuels such as butanol and biodiesel.

Another vein of research concerns the production of plastics, including, in one project, nylon for stockings. Nylon, a polymer, is made up of two different components derived from petroleum products. Its traditional production is energy intensive, results in toxic by-products and is reliant on the price of oil. Martin’s research looks at how to get yeast to produce the two starting molecules. “We don’t need to rely on oil and gas anymore,” says Martin. “We can get organisms to take carbon dioxide, or glucose, and make these molecules.”

He also works on molecules that are used by the pharmaceutical industry, including painkillers and opiates, and alkaloids used to treat cancer and heart disease. “Our competition is the big Ivy League schools,” says Martin. “We’re really at the forefront of this research.”

Unknown molecules

One researcher is Lauren Narcross, BSc 10, a current PhD student in Martin’s lab. Working with yeast, she produces molecules with a pharmaceutical application. The goal of the project is to expand the total number of molecules available for research in the world.

Lauren Narcross Lauren Narcross earned a BSc in cellular and molecular biology from Concordia in 2010 and is now a PhD student at the centre for applied synthetic biology working with yeast to engineer the production of molecules with a wide range of pharmaceutical applications.

Poppies, Narcross explains, are really good at making a few compounds — such as morphine, noscapine, papaverine, codeine and sanguinarine — that have been developed into pharmaceuticals such as painkillers, muscle relaxants and cough suppressants.

Unfortunately poppies are not as good at making thousands of other compounds, which are therefore greatly understudied. By taking the genes that make these compounds from the poppy and other plants and putting them into yeast, Narcross and fellow researchers at the synthetic biology centre hope the yeast will make a high number of those molecules and provide an alternative source for them. She reports that there are 2,500 molecules identified or predicted in a variety of plants, not just the poppy, that are potentially of interest. “The goal of the project is to create an alternative technology that will allow pharmaceutical companies to study these other compounds,” says Narcross.

Researchers at the centre work with a lab that grows and tests opium poppies. “We’re really good at the ‘working in yeast’ part,” she says.

Robots in the lab

To conduct the research, Narcross and her colleagues must take the identified genes out from the plants — including poppies — and put them into yeast to see if they will start producing a lot of the desired molecule. However, this process is difficult, time-consuming, tedious and unpredictable.

Luckily, automation of that process is coming soon. A $2.5-million grant from the Canada Foundation for Innovation to develop a biofoundry at the centre means a good deal of new equipment that will help researchers make and manipulate DNA. “There’s a lot of automation that can be put into place to give our scientists, who are trained in how to think, more freedom,” says Narcross.

She was awaiting the arrival of the biofoundry’s first piece. “I’m really excited to see this technology completely change the research we do here,” she says. “The process is very satisfying. We get to problem-solve for a living. It’s cool to be making molecules that can make a difference to people.”

“We get to problem-solve for a living. It’s cool to be making molecules that can make a difference to people.” “We get to problem-solve for a living. It’s cool to be making molecules that can make a difference to people.”

Standardization is one of the goals of the centre under Martin. “That way, you’re hoping the outcome is very predictable. You want to be able to go around the design-build-test-learn loop as fast as possible.”

Martin says that a testament to the centre’s work is its ability to attract world-class researchers in the field of synthetic biology. One is Steve Shih, who builds microfluidics — or labon-chip technology. “If my research is successful, we’ll be able to program an experiment on a computer that will automate the process on a chip,” Shih says. “It could take days or weeks when a researcher conducts the experiment manually. On the chip, it takes a few hours,” which means saving time and money for other research.

Shih studied engineering but did his postdoctorate in a synthetic biology lab. “This centre was the only place in Canada where I could research microfluidics, do the engineering, work on the chemistry and study the biology at the same time. That’s what attracted me,” he says. “I have an interdisciplinary background and I wanted to be in an interdisciplinary environment, so I thought it was a perfect match.”

He’s currently working on microfluidics projects with both Martin and the centre’s co-director and co-founder, Nawwaf Kharma.

A fundamentally multidisciplinary initiative

Kharma, an associate professor in the Department of Electrical and Computer Engineering, sees the centre’s multidisciplinary team as one of its greatest assets. “A high density of highly qualified people all working in the same area — that’s what will guarantee we’ll get very good research done,” he says. “When you get so many good people, like our recent hires, into a very well defined area — in this case, synthetic biology — and they share lab space, meet regularly and have inspiring leadership, it works very well.”

His path from engineering into synthetic biology is a novel one. “I was doing research in evolutionary computing already, so I thought, I’ll just learn a bit more about evolution,” he explains. That was just the beginning.

Kharma took a course at Concordia in molecular biology and became friends with the prof, Luc Varin, BSc 87, PhD 91, an associate professor in the Department of Biology and now also a member of the centre. Through Varin, Kharma met Martin and became increasingly interested in how he could apply computational engineering to biology.

Kharma also signed up for a master’s degree in biology, which he’s completing this year. Though he’s found it demanding, he says the structured learning was invaluable to his biology knowledge.

Martin too is a classically trained biologist, although his postdoctoral research was in an engineering department — which makes the co-directors a good match. “I spent enough time with engineers to realize their thought process is completely different from biologists,” says Martin. “It’s a lot more structured, in most instances, and to me it was very important to have that aspect in the centre. Nawwaf certainly brings that.”

He adds that the centre’s biologists recognize real-world boundaries of what’s physically doable, as opposed to what calculations or models theoretically show what’s possible. That includes Malcolm Whiteway, a professor in the Department of Biology and Canada Research Chair in Microbial Genomics, Biology. His research concerns the fungal pathogen Candida albicans, and the new biofoundry will be crucial to several projects he leads.

Whiteway sees many benefits to the centre’s multidisciplinary nature. “It’s good to be able to talk to smart people who have different backgrounds than you do about questions that are of relevance to you because they can provide novel insights,” Whiteway says. “Being able to direct your grad students to the Martin lab on a question, for example, is extremely useful.”

He points out that one of the centre’s mandates is to spread knowledge about synthetic biology. “It’s not just about researchers,” Whiteway says. “There’s also a journalistic element regarding ethics and how the information is presented to the general public.”

Whiteway refers to David Secko, an associate professor in the Department of Journalism and centre member. Secko, who trained as a molecular biologist before becoming a science journalist, studies and promotes biotech literacy to the general public. He recently hosted a panel discussion regarding CRISPR, a new technology for editing genes that’s raised a number of ethical questions.

Another centre member, Tagny Duff, MFA (studio art) 05, PhD 14, associate professor in the Department of Communication Studies, uses biology as a medium for design and art. She’s currently working on a project that will be displayed at the Centre for Structural and Functional Genomics on the Loyola campus, where the centre is located.

Like Whiteway, Martin sees a need to educate the general public about synthetic biology. “Go out there and try to engage. Describe what it is you’re doing, along with the potential benefits and pitfalls,” he says. “It’s a really interesting way to bring synthetic biology into popular culture.”

A changing field

Corinne Cluis Corinne Cluis’s Concordia PhD research was on the coenzyme q10, an antioxidant that’s been shown to alleviate symptoms related to heart diseases, diabetes and neurological disorders.

Because the field of synthetic biology is growing and changing exponentially, it’s crucial to train graduate students how to think and be creative, says Martin. “That way they can use that expertise wherever they end up.”

Corinne Cluis, PhD 14, knew pretty early on in her career that she wanted to translate what she liked about research and biology into products that were useable for society. As a PhD student in Martin’s lab, she produced coenzyme Q10, an antioxidant that’s been shown to alleviate symptoms related to heart diseases, diabetes, Parkinson’s and Alzheimer’s. It’s also well known as an anti-wrinkle agent. The goal was to produce the molecule cheaply, using a non-pathogenic form of the bacteria E. coli and cheap substrates like glucose. Cluis managed to multiply the production of Q10 in E. coli 20 times.

Today she works in the strain development lab at Lallemand in Montreal, a company that specializes in producing yeast and bacteria products needed to make wine, animal feed, nutritional products, probiotics, biofuels and baking and food products. There is a cohort of four or five former students of

Martin’s working at the company. Cluis says the centre and Martin were crucial to the scope and success of her project: “He gave me a lot of freedom to think about my project, to try different things, to give it the direction that I wanted.” Martin also challenged Cluis to do the best she could. “He was also great at making me push boundaries, and encouraging me to be ambitious, not to do things that have been done in the past or that weren’t very original.”

A lot has changed in synthetic biology since 2014, but Cluis says what she does now is a direct application of what she learned during her PhD. “My way of thinking, trouble shooting and approaching research projects was really developed through my interactions with Dr. Martin.”

Martin hopes that’s the case. “What I can bring to my students, having spent and still spending time with these companies, is that I understand how they work, I understand what they’re looking for,” he says. Martin himself co-founded Amyris, a renewable products company that provides sustainable alternatives to a range of petroleum-sourced products. He continues to serve as its scientific advisor.

The future

The centre is looking at developing programs for engineers and biologists, and that means crossing departments and faculties.

To do this, Kharma and Martin are applying for an educational Collaborative Research and Training Experience (CREATE) Program grant from the Natural Sciences and Engineering Research Council of Canada. “It’s the best way we can leverage our expertise into a training program,” says Kharma. “It’s not a degree program; it uses existing structures and courses to train somebody in a particular area. That way our research will benefit teaching.”

Martin adds, “You have to build your academic programs to be adaptable and flexible so that when things change you can modify them.”

What will future research in Martin’s lab look like? Some projects will be moving into non-model systems. “We’re starting to biologically engineer things that people have never engineered before: different types of micro-organisms, different types of yeast,” he says.

Automating more and more of the lab processes is also a priority. “The biofoundry is going to be a big part of developing tools and technology to speed things up. This is where it’s heading,” Martin says. “We’re all going to be on computers, building, designing and creating biological systems and pushing a button and some assembly line somewhere will build it.”

His aspirations go beyond the centre. “Our hope is to get the seeds of automation going here at Concordia, and we want to push that into a national platform,” Martin says. “It’s not just for my lab. It’s for labs across the university, province and country.”

— Vanessa Bonneau is a Montreal freelance writer and editor

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